Membranoproliferative Glomerulonephritis: A Prospective Clinical Trial of Platelet-Inhibitor Therapy

Forty patients with Type I membranoproliferative glomerulonephritis were treated for one year with dipyridamole, 225 mg per day, and aspirin, 975 mg per day, in a prospective, randomized, double-blind, placebo-controlled study. At the base line, the half-life of 51 Cr-labeled platelets was reduced in 12 of 17 patients. The platelet half-life became longer and renal function stabilized in the treated group, as compared with the placebo group, suggesting a relation between platelet consumption and the glomerulopathy. The glomerular filtration rate, determined by iothalamate clearance, was better maintained in the treated group (average decrease, 1.3 ml per minute per 1.73 m 2 of body-surface area per 12 months) than in the placebo group (average decrease, 19.6). Fewer patients in the treated group than in the placebo group had progression to end-stage renal disease (3 of 21 after 62 months as compared with 9 of 19 after 33 months). The data suggest that dipyridamole and aspirin slowed the deterioration of renal function and the development of end-stage renal disease. (N Engl J Med 1984; 310:1421–6.) MEMBRANOPROLIFERATIVE glomerulonephritis is a primary glomerular disease with distinct morphologic patterns. It affects children and adults, is poorly understood, and is associated with a high but variable rate of progression to renal failure. 1 2 3 4 5 6 Contrary to uncontrolled studies, 7 8 9 three randomized controlled trials showed no beneficial effects on renal function and glomerular morphologic features after treatment with prednisone 10 or a combination of cyclophosphamide, dipyridamole, and warfarin sodium. 11 , 12 The rationale for the use of platelet-inhibitor drugs in glomerulonephritis stems from the demonstrations of platelet activation in glomerulonephritis, 13 14 15 arterial smooth-muscle-cell proliferation by platelet factors, 16 and increased platelet consumption in various vascular 17 18 19 and renal 20 21 diseases, . . .